What is the genetics of epilepsy?
Epilepsy is a chronic neurological disorder whose etiology, in more than half of the cases, is genetic. This disease is characterized by sudden recurrent seizures, loss of consciousness and convulsions.
Various epidemiological studies have shown that the hereditary factor plays a major role in this respect.
However, in most patients affected by common epileptic syndromes no specific genetic cause has been determined, since most syndromes follow a complex pattern of inheritance.
This means that multiple genes are involved whose exposure to certain environmental factors give rise to epileptic syndromes.
What tests are performed for diagnosis?
Studies focus on the analysis of genes involved in the functioning of ion channels. As a result, regions considered to be of importance in the pathogenesis of generalized epilepsies are located mainly on chromosomes 0139-313.3.
The most traditionally used sequencing method is the Sanger method. It is a very reliable method, but at the same time very slow because of the individual analysis of the genes of interest.
With the advent of technology, this process has been accelerated and massive portions of DNA can be analyzed in a shorter time. Genetic analysis identifies copy number variations (CNVs) in the form of duplication of portions of DNA or single nucleotide polymorphisms (SNPs).
The technology has also made it possible to identify new genes associated with epilepsy. Specifically, more than 900 epilepsy-associated genes have been identified, of which about 84 cause epilepsy as the main symptom.
Limitations of diagnostic tests
Despite the many benefits that the inclusion of technology in the analysis and diagnosis of epilepsy due to genetic causes can bring us, there are still limitations.
Among them are the high economic cost, the results depend on the quality of the laboratory and the waiting time for the results is long.
Other factors limiting the genetic study of epilepsy are:
- Incomplete penetrance. That is to say, despite the presence of the allele predisposing to the disease, it is possible that it does not present clinical manifestation.
- Mutations of different genes that result in the same phenotype.
- Multifactorial. The manifestation of epilepsy responds to genetic and environmental factors.
What does the test consist of? Who is it aimed at?
The test is performed on the basis of genomic DNA analysis and the massive NGS sequencing panel for genetically based epilepsies is applied. Next Generation Sequencing (NGS) is a diagnostic alternative to sequencing using the Sanger method and guarantees the representativeness of the regions of interest as well as maximum diagnostic sensitivity and specificity.
It is mainly aimed at patients who present epilepsy of genetic origin and have not identified a phenotype that allows the genetic study of a specific gene.
What information does the test provide?
This study, among other things, makes it possible to establish an early diagnosis of epilepsy, which in children’s cases is of vital importance. It also makes it possible to determine the most appropriate type of pharmacological treatment and, therefore, a better prognosis and evolution.
Which specialist treats it?
The neurologist will be the specialist in charge of the treatment of epilepsy, since he/she is a physician specialized in the study of diseases and disorders affecting the nervous system.